Foodborne fungus impairs intestinal wound healing in Crohn’s disease – Washington University School of Medicine in St. Louis

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In a study on mice, humans propose new approaches to treating symptoms

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Eating is a dangerous business. Naturally occurring toxins in food and potentially harmful microbes in food can have a number of effects on our gut, resulting in repeated minor injuries. In healthy people, such damage usually heals in a day or two. In people with Crohn’s disease, the wounds fester, causing abdominal pain, bleeding, diarrhea, and other uncomfortable symptoms.

Researchers at Washington University St. Louis Medical School and the Cleveland Clinic have found that a fungus found in foods like cheese and processed meat can infect intestinal damage sites and prevent healing in mice and people with Crohn’s disease. In addition, treating infected mice with antifungal drugs clears the fungus and allows the wounds to heal.

The results, published March 12 in the journal Science, suggest that antifungal drugs and dietary changes are potential new approaches to improving bowel wound healing and reducing symptoms of Crohn’s disease.

“We’re not suggesting that people stop eating cheese and processed meat. That would be way beyond what we currently know, ”said lead author Umang Jain, PhD, professor of pathology and immunology at the School of Medicine. “We know that this food-borne fungus can get into inflamed, injured tissue and cause damage. We plan to do a larger study in humans to see if there is a link between diet and the abundance of this fungus in the gut. In this case, it is possible that dietary changes could lower the levels of fungi, thereby reducing the symptoms of Crohn’s disease. “

Crohn’s disease is a subtype of inflammatory bowel disease. As the name suggests, it is triggered by chronic inflammation in the digestive tract and is mainly treated with immunosuppressive drugs. Crohn’s patients suffer from repeated cycles of gastrointestinal symptoms and remission. During a torch, your digestive tracts are littered with inflamed, open sores that can last for weeks or even months.

To understand why colon ulcers take so long to heal in some people, Jain and senior author Dr. med. Thaddeus Stappenbeck, formerly at Washington University and now at the Cleveland Clinic, mice whose intestines had been injured. By sequencing microbial DNA at the site of the injury, they discovered that the fungus Debaryomyces hansenii was abundant in wounds but not in uninjured parts of the intestine.

People get the mushroom through their food and drink, Jain said. D. hansenii is common in all types of cheese, as well as sausage, beer, wine, and other fermented foods.

Further experiments showed that introducing the fungus into mice with injured intestines slowed the healing process and that the elimination of D. hansenii with the antifungal amphotericin B accelerated it.

People with Crohn’s disease carry the same fungus as the mice. Jain and Stappenbeck examined intestinal biopsies from seven people with Crohn’s disease and ten healthy people. All seven patients had the fungus in their intestinal tissues compared to just one of the healthy people. In a separate analysis of 10 Crohn’s patients with tissue samples from both inflamed and non-inflamed areas of the intestine, the researchers found the fungus in samples from all patients, but only in areas of injury and inflammation.

“If you look at stool samples from healthy people, this fungus is very common,” Jain said. “It goes in your body and comes out again. However, people with Crohn’s disease have a defect in the intestinal barrier that allows the fungus to invade the tissue and survive there. And then it feels at home with ulcers and foci of inflammation, preventing those areas from healing. “

The results suggest that getting rid of the fungus could restore normal wound healing and shorten flare-ups. While the drug amphotericin B was effective in eliminating the fungus in mouse studies, it is not widely used in humans because it can only be given intravenously. The researchers are working with chemists to develop a powerful antifungal that can be taken orally. They also investigate whether there is a link between diet and the amount of the fungus in people’s digestive tracts.

“Crohn’s disease is basically an inflammatory disease. Even if we figured out how to improve wound healing, we wouldn’t cure the disease,” Jain said. “But in people with Crohn’s disease, impaired wound healing causes a lot of suffering. If we can show that depletion of this fungus in people’s bodies – either through diet changes or through antifungal drugs – can improve wound healing, it can affect quality of life in ways that we have not been able to achieve with more traditional approaches. ”

Jain U, Ver Heul AM, Xiong S., Gregory MH, Demers EG, Kern JT, Lai CW, Muegge BD, Barisas DAG, Leal-Ekman JS, Deepak P., Ciorba MA, Liu TC, Hogan DA, Debbas P. , Braun J., McGovern DPB, Underhill DM, Stappenbeck TS. Debaryomyces is accumulated in the intestinal tissue of Crohn’s disease and interferes with healing in mice. Science. March 12, 2021. DOI: 10.1126 / science.abd0919

The study was supported by the Crohn’s & Colitis Foundation; Lawrence C. Pakula; IBD innovation; the National Institutes of Health (NIH), Grant Numbers AT009741, AI127548, DK125296, and NIH DK46763; the US Department of Veterans Affairs, Grant Number IK2BX004909-01; and the American College of Gastroenterology.

The 1,500 faculty physicians at Washington University School of Medicine are also medical staff at Barnes-Jewish and St. Louis Children’s Hospitals. The School of Medicine is a leader in medical research, teaching, and patient care and is among the top 10 medical schools in the country according to the US News & World Report. The School of Medicine is affiliated with BJC HealthCare through its affiliation with the Barnes-Jewish and St. Louis Children’s Hospitals.

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